Morita enantioselective

The highly enantioselective Morita-Baylis-Hillman reaction of cyclohexenone with aldehydes is catalyzed by a chiral BlNOL-derived Brpnsted acid 8 in the presence of triethylphosphine as the nucleophilic promoter (Scheme 12.6). ... 

A series of A - / - n i trobe nzenesul fony 1 imincs have been reported to undergo asymmetric aza-Morita-Baylis-Hillman reactions with methyl acrylate mediated by DABCO in the presence of chiral thiourea organocatalysts with unprecedented levels of enantioselectivity (87-99% ee), albeit only in modest yields (25 19%). Isolation of a DABCO-acrylate-imine adduct as a key intermediate, kinetic investigation, and isotopic labelling, have been employed to determine the mechanism.177... 

A highly enantioselective proline-catalysed intramolecular Morita-Baylis-Hillman reaction of hept-2-enedial (111) has been reported. Addition of imidazole to the mixture resulted in an unusual inversion of enantioselectivity.149 The first example of a TiCU-mediated Morita-Baylis-Hillman-type reaction of cy-acetyl cyclic ketene dithioacetals with arylaldehydes has been described.150... 

Another class of bifunctional organocatalysts for the enantioselective aza-Morita-Baylis-Hillman reaction of imines (112) with enones (113) (Scheme 6) is based on BINOL (115). The efficiency of the catalysts proved to be mainly influenced by the position of the Lewis basic moiety attached to the BINOL scaffold. The activation of the substrate by acid-base functionalities and the fixing of conformation of the catalyst (115) are apparently harmonized to maximize the enantiocontrol (<95% ee) 52... 

Organocatalytic Enantioselective Morita-Baylis-Hillman Reactions... 

Organocata lytic Enantioselective Morita-Baylis-Hillman Reactions Table 5.4 MBH reaction of aryl aldehydes and MVK catalyzed by /MCD. 

Akiyama T, Morita H, Itoh J, Fuchibe K (2005a) Chiral Brpnsted acid catalyzed enantioselective hydrophosphonylation of imines asymmetric synthesis of alpha-amino phosphonates. Qrg Lett 7 2583-2585 Akiyama T, Saitoh Y, Morita H, Fuchibe K (2005b) Enantioselective Mannich-type reaction catalyzed by a chiral Bronsted acid derived from TADDOL. Adv Synth Catal 347 1523-1526... 

Scheme 13.26 Model proposed to explain the origin ofthe enantioselectivity. (Source E.L. Myers. J.C. de Vries, V.K. Aggarwal, Reactions of iminium ions with Michael acceptors through a Morita Baylis Hillman...

The Pd complexes of (R R,R)-3Sh were found to be highly efficient in the enantiose-lective allylic amination of the esters of racemic Morita-Baylis-Hillman (MBH) adducts with aromatic amines, affording optically active P-arylamino acid esters in high activity (TON up to 4750) with high region- and enantioselectivities (Scheme 53)... 

Chen and coworkers employed the cinchona alkaloid-derived catalyst 26 to direct Mannich additions of 3-methyloxindole 24 to the A-tosylimine 25 to afford the all-carbon quaternary center of oxindole 27 with good enantioselectivity (84% ee) [22]. The outcome of this Mannich reaction is notable in that it provided very good selectivity for the anti diastereomer (anti/syn 94 6). The mechanism of asymmetric induction has been suggested to involve a hydrogen bonding network between the cinchona alkaloid 26, the oxindole enolate of 24, and the imine electrophile 25 (Scheme 7). Asymmetric allylic alkylation of oxindoles with Morita-Baylis-Hillman carbonates has been reported by the same group [23]. 

Bifunctional organocatalysts, particularly, (S)-3-(N-isopropyl-N-3-p5nidi-nylaminomethyl) BINOL for enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reactions 07Y1089. 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

Scheme 7.28 Enantioselective Michael/Morita-Baylis-Hillman cascade reaction.

Shi et al7 reported a highly enantioselective allylic substitution of Morita-Baylis-Hillman (MBH) acetate with TMSOF that could be achieved by chiral prolinamide phosphane organocatalysts 43 in good yield and high ee. 

The P-chirogenic organocatalysts 294 and 295 were found to promote the enantioselective aza-Morita-Bayhs-Hillman reaction of ketimines derived from acyclic a-keto esters. In the P-chirogenic organocatalyzed aza-Morita-Baylis-Hillman reactions, a,a-disubstituted a-amino acid derivatives 296 were obtained in high yields and with high enantioselectivities (up to 97% cc) (Scheme 98) [195]. 

Scheme 98 The organocatalytic enantioselective aza-Morita-Baylis-Hillman reaction O...

The Wang group also realized enantioselective oxidative cross-coupling reactions between tertiary amines and the activated olefins by merging Cu(OTf)2 with quinine as the best cooperative catalysts/ A Morita-Baylis-Hillman-type mechanism is in operation. It was notable that molecular oxygen was employed as the sole oxidant. As shown in Scheme 2.12, the reactions between Ai-aryl THIQs and the a,p-unsaturated aldehydes or ketones 30 proceeded smoothly to afford the a-functionalized products 31 in up to 81% yield and 99% ee. 

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